The goal of this Phase II SBIR project is to develop and validate an efficient and consistent selective stimulator to assess A-delta and C fiber pain sensing neurons (nociceptors) for use with human volunteers for new drug evaluation and with pain patients to aide in diagnosis. There is currently no commercially available tool of similar capabilities on the market. Evaluation of thermal pain sensitivity in humans can be useful in describing the potential utility of putative analgesic drugs. The ability to reliably, differentiate pain mediated by the activation of unmyelinated (C) or myelinated (A-delta) nociceptors may also provide allow for more accurate prediction of the efficacy of pain treatments. There is also a potential utility of being able to differentially as certain pain mediated by these two afferent types in establishing a diagnosis for, and following the progress of patients in pain. Thus, it is our overall goal to establish stimulation protocols for use with our unique infrared diode laser that will allow, in humans, for the differential assessment of pain evoked by the activation of these two nociceptor types, and to test these protocols using benchmark pharmacologic agent. Thus, we hypothesize that the infrared diode laser will prove safe and reliable, such that it, and its components will be certifiable for meeting FDA requirements for non-invasive skin heating. To do this, we will determine the stimulus intensity margin between pain threshold measurement and skin damage. In addition, we will insure complete compatibility of the laser with functional magneto-resonance imaging systems and EEG cortical evoked potential recording systems, making any hardware and software adjustments that are necessary. We will also submit the laser and its components for certification as to electrical and magnetic interference and for medical laser safety standards, and make any device changes that are necessary to meet the requirements. We will also insure that the device protocols will allow for accurate and differential assessment of proalgesic and analgesic effects of drugs known to differentially affect C or A-delta nociceptors, including the TRPV1 agonist capsaicin, the A-delta sensitizing solvent dimethyl sulfoxide (DMSO), and the mu opioid analgesic morphine. To do this, we will assess psychophysical and cortical (EEG) responses evoked by brief pulses that activate A-delta nociceptors, or longer pulses that activate C fiber nociceptors. [unreadable] [unreadable] [unreadable]